Peripheral artery disease (PAD) is an atherosclerotic disease with narrowing blood vessel lumen, and is often associated with diabetes due to elevated blood sugar level. If left untreated, PAD can lead to blockage of vessels, resulting in tissue death and possible amputation of a limb. About 10 million Americans are affected by lower extremity PAD. Among other risks, the risk of PAD is markedly increased among subjects with diabetes, the 7th leading cause of death in the U.S. The rate of ischemic events is higher in diabetic individuals with PAD than in comparable non-diabetic populations. Current tools for diagnosing and monitoring PAD in diabetic patients rely on ankle-brachial index (ABI). However, ABI has a low sensitivity of detecting PAD and may not reveal a large proportion of asymptomatic patients with hidden stenosis of PAD. Currently, CT angiography (CTA) has gained wide acceptance that is preferred by vascular surgeons due to simple, fast, diagnostic and reproducible image quality, and less invasive for detecting PAD. Nevertheless, repeated PAD CTA examinations are not desired from the safety concerns like long ionizing radiation exposure and high dose iodine contrast medium. A safe and robust imaging modality, which can accurately visualize the entire peripheral vasculature, is critically in need. Non-contrast magnetic resonance angiography (NC-MRA), without a Gadolinium contrast injection, non-invasiveness, and non-radiation would be an ideal diagnostic and follow- up tool for diabetic patients with and without PAD. Current NC-MRA techniques permit depiction of entire peripheral vascular imaging; however, there are following limitations in current NC-MRA as compared to CTA: inferior spatial resolution, prolong examination time, non-reproducible diagnostic image quality, artifacts, and limitation in follow-up of PAD patients with surgical devices such as stents and bypass grafts. The project aims to develop an advanced fresh-blood imaging (FBI) for fast, safe, robust, diagnostic, reproducible NC-MRA and an innovative, free-breathing, ungated, non-subtracted NC-MRA technique using 3D ultra-short TE (UTE) for follow up on the patients with surgical devices. In addition, micro-vascularity of diabetic foot will be investigated using a new non-contrast MR perfusion (NC-MRP) technique. This five-year project consists of an initial two- year technical development and optimization, followed by a clinical assessment study that will validate both advanced FBI, 3D UTE, and NC-MRP on diabetic patients with and without PAD regardless of the presence of surgical devices.
Our specific aims are as follows:
Aim 1 A: To develop an advanced FBI with centric ky-kz trajectory with a new exponential refocusing flip angle;
Aim 1 B: To develop the free-breathing, ungated, non- subtraction 3D UTE NC-MRA technique;
Aim 2 : To develop the NC-MRP technique to measure micro- vascularity of the foot;
and Aim 3 : To compare the diagnostic accuracy of advanced FBI and 3D UTE developed in Aims 1 and evaluate micro-vascularity by NC-MRP in Aim 2 on diabetes with or without PAD with CTA/DSA. We will also correlate micro-vascularity measures with various diabetic levels of HbA1c and ABI.

Public Health Relevance

Peripheral artery disease (PAD) affects about 10 million people and diabetic PAD is the 7th leading cause of death in the United States; development of fast, robust, diagnostic non-contrast MR angiography (NC-MRA) and non-contrast MR perfusion (NC-MRP) methods is essential to image lower extremity arteries and the blood supply to distal foot. Safe and repeatable NC-MRA techniques for diagnosis and follow-ups of PAD patients regardless of the presence of surgical devices would have a significant impact over CTA associated with risks like ionizing radiation exposure and allergic reactions to contrast materials. The project aims to develop an advanced fresh-blood imaging and an innovative, free-breathing, ungated, non-subtraction 3D ultra-short TE NC-MRA, and the new NC-MRP technique to study micro-vascularity of the diabetic foot for safe, robust, diagnostic, reproducible NC-MRA without concerns of radiation exposure and contrast injection.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Emerging Imaging Technologies and Applications Study Section (EITA)
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Danthi, Narasimhan
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University of California, San Diego
Schools of Medicine
La Jolla
United States
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